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This study investigated whether vitamin A (VA) administration during the neonatal stage could increase the number of intramuscular adipocytes in Hu sheep by promoting vascularity. A total of 56 newborn male Hu sheep were divided into four groups and received intramuscular injections of either 0, 7500 IU retinoic acid (RA), 7500 IU VA, or a combination of 7500 IU VA and 5 mg SU5416 (an angiogenic inhibitor), at 1, 7, 14, and 21 days of age. At 15 days of age, 6 sheep from each group were randomly selected and sacrificed for intramuscular adipogenic capacity analysis. The remaining 8 sheep in each group were raised until they were 8 months old. VA-treated sheep exhibited an increase in preadipocytes, elevated expression of adipogenic genes (CCAAT enhancer binding protein alpha [CEBPA] and CCAAT enhancer binding protein beta [CEBPB]) and angiogenic genes (vascular endothelial growth factor A [VEGFA]), and stromal vascular fraction cells in the longissimus dorsi (LD) muscle with enhanced adipogenic capacity (P ＜ 0.05). These effects were entirely negated by SU5416. Upon slaughter, VA increased final weight, carcass weight, and average daily gain (P ＜ 0.05) but did not affect feed intake at 21 to 32 weeks (P = 0.824). VA increased the number of intramuscular adipocytes in the LD and semitendinosus (ST) muscle (P ＜ 0.05) without changing the adipocyte number of the omentum, perirenal and subcutaneous fats (P ＞ 0.05). VA injections also increased intramuscular triglyceride (TG) content (P = 0.016) without changing the omentum fat weight or subcutaneous fat thickness (P ＞ 0.05), but it did increase the perirenal fat weight (P = 0.011). Consistently, SU5416 mitigated the effects of VA on intramuscular TG content and adipocyte count, correlating with a decrease in vascularity. In contrast, RA injections didn't affect the intramuscular fat (P = 0.744) but reduced the TG content of the omentum and perirenal fat (P ＜ 0.05). In conclusion, intramuscular injections of VA but not RA at the neonatal stage improved the growth performance of Hu sheep, increasing the number of intramuscular adipocytes and marbling by promoting angiogenesis.

Abstract Background Current guidelines recommend maintaining a resting heart rate below 100–110 beats per minute (bpm) for patients with atrial fibrillation (AF). However, there is a lack of research on various treatment approaches for patients with both atrial fibrillation and coronary heart disease (AF&CHD). We have discussed the primary therapeutic options for controlling resting heart rate in patients with AF&CHD. Methods We conducted a post hoc analysis of the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial. Our study included 3986(98.2%) participants with AF, of which 1522 had AF&CHD. The primary outcome was all-cause mortality. We utilized the chi-squared test to identify significant differences in categorical variables. Multivariate Cox regression analysis was performed to compare the risk of death by standard deviation of heart rate visit to visit variability quartile. Results Compared to the AF group, a higher proportion of patients in the AF&CHD group had histories of smoking, hypertension, diabetes, heart failure, cardiomyopathy, valvular heart disease, peripheral vascular disease, bradycardia, hepatic or renal disease, pulmonary disease, and stroke (all P

Intestinal stem cells (ISCs) initiate intestinal epithelial regeneration and tumorigenesis, and they experience rapid refilling upon various injuries for epithelial repair as well as tumor reoccurrence. It is crucial to reveal the mechanism underlying such plasticity for intestinal health. Recent studies have found that metabolic pathways control stem cell fate in homeostasis, but the role of metabolism in the regeneration of ISCs after damage has not been clarified. Here, we find that in a human colorectal cancer dataset, miR-29a and b (miR-29a/b) are metabolic regulators highly associated with intestinal tumorigenesis and worse prognostic value of radiotherapy. We also show that these two microRNAs are required for intestinal stemness maintenance in mice, and their expression is induced in regenerated ISCs after irradiation injury, resulting in skewed ISC fate from differentiation towards self-renewal. This upregulation of miR-29a/b expression in ISCs leads to suppression of fatty acid oxidation (FAO) and depression of oxidative phosphorylation, which in turn controls the balance between self-renewal and differentiation of ISCs. Deletion of miR-29a/b prevents these effects and thus impairs ISC-mediated epithelial recovery. Finally, we filter the potential targets of miR-29a/b and identify Hnf4g, a transcription factor, that drives this metabolic reprogramming through regulating FAO-related enzymes. Our work discovers an important metabolic mechanism of ISC-mediated regeneration and potentially pave the way for more targeted and effective therapeutic strategies for intestinal repair as well as tumor treatment.

Abstract Background The effects of anesthetics on liver and kidney functions after infantile living-related liver transplantation (LRLT) are unclear. This study aimed to investigate the effects of propofol-based total intravenous anesthesia (TIVA) or desflurane-based inhalation anesthesia on postoperative liver and kidney functions in infant recipients after LRLT and to evaluate hepatic ischemia–reperfusion injury (HIRI). Methods Seventy-six infants with congenital biliary atresia scheduled for LRLT were randomly divided into two anesthesia maintenance groups: group D with continuous inhalation of desflurane and group P with an infusion of propofol. The primary focus was to assess alterations of liver transaminase and serum creatinine (Scr) levels within the first 7 days after surgery. And the peak aminotransferase level within 72 h post-surgery was used as a surrogate marker for HIRI. Results There were no differences in preoperative hepatic and renal functions between the two groups. Upon the intensive care unit (ICU) arrival, the levels of aspartate aminotransferase (AST, P = 0.001) and alanine aminotransferase (ALT, P = 0.005) in group P were significantly lower than those in group D. These changes persisted until the fourth and sixth days after surgery. The peak AST and ALT levels within 72 h after surgery were also lower in group P than in group D (856 (552, 1221) vs. 1468 (732, 1969) U/L, P = 0.001 (95% CI: 161–777) and 517 (428, 704) vs. 730 (541, 1100) U/L, P = 0.006, (95% CI: 58–366), respectively). Patients in group P had lower levels of Scr upon the ICU arrival and on the first day after surgery, compared to group D (17.8 (15.2, 22.0) vs. 23.0 (20.8, 30.8) μmol/L, P

Abstract Background Previous studies only considered the impact of a single physical or psychological disorder on dementia. Our study investigated the association of physical and psychological multimorbidity with dementia among older adults using two multinational prospective cohorts to supplement the limited joint evidence. Methods We utilized the Health and Retirement Study (HRS 2012 to 2018) in the United States (US) and the Survey of Health, Ageing and Retirement in Europe (SHARE 2012 to 2018). Physical disorder was defined as any one of seven self-reported physician-diagnosed conditions. Psychological disorder was assessed using the 8-item Center for Epidemiologic Research Depression (CES-D) scale or the EURO-D. Dementia was determined through a combination of self-reported physician diagnosis of dementia or Alzheimer’s disease, or the 27-point HRS cognitive scale. Competing risk models were utilized to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CI). DerSimonian-Laird random-effects meta-analyses were conducted to obtain pooled estimates. Results The prevalence of physical and psychological multimorbidity was 17.29% (1027/5939) in continental Europe and 15.52% (1326/8543) in the US. The incidence of dementia was 6.21 per 1000 person-years in continental Europe and 8.27 per 1000 person-years in the US, respectively. It was highest among participants with physical and psychological multimorbidity in continental Europe (10.46 per 1000 person-years) and the US (14.82 per 1000 person-years), compared with the other three groups. In the univariate model, participants who reported physical and psychological multimorbidity had a higher risk of dementia compared with those who reported no physical and psychological disorders in continental Europe (HR = 2.59; 95% CI: 1.55, 4.33) and the US (HR = 4.11; 95% CI: 2.44, 6.94). After adjusting all covariates, the risk of dementia among participants who reported physical and psychological multimorbidity increased by 86% in continental Europe (aHR = 1.86; 95% CI: 1.08, 3.21) and by 176% in the US (aHR = 2.76; 95% CI: 1.61, 4.72), respectively. After pooling the outcomes, the risk of dementia among participants who reported physical and psychological multimorbidity increased by 115% (aHR = 2.15; 95% CI: 1.27, 3.03). Conclusions Physical and psychological multimorbidity was prevalent among older adults in the US and continental Europe. Given the consistent associations with dementia, it is imperative to increase awareness of the links and recognize the limitations of single-disorder care. Specific attention should be given to providing care coordination.

Abstract Background Chronic kidney disease (CKD) is a significant risk factor for pulmonary hypertension (PH), a complication that adversely affects patient prognosis. However, the mechanisms underlying this association remain poorly understood. A major obstacle to progress in this field is the lack of a reliable animal model replicating CKD-PH. Methods This study aimed to establish a stable rat model of CKD-PH. We employed a combined approach, inducing CKD through a 5/6 nephrectomy and concurrently exposing the rats to a high-salt diet. The model's hemodynamics were evaluated dynamically, alongside a comprehensive assessment of pathological changes in multiple organs. Lung tissues and serum samples were collected from the CKD-PH rats to analyze the expression of angiotensin-converting enzyme 2 (ACE2), evaluate the activity of key vascular components within the renin–angiotensin–aldosterone system (RAAS), and characterize alterations in the serum metabolic profile. Results At 14 weeks post-surgery, the CKD-PH rats displayed significant changes in hemodynamic parameters indicative of pulmonary arterial hypertension. Additionally, right ventricular hypertrophy was observed. Notably, no evidence of pulmonary vascular remodeling was found. Further analysis revealed RAAS dysregulation and downregulated ACE2 expression within the pulmonary vascular endothelium of CKD-PH rats. Moreover, the serum metabolic profile of these animals differed markedly from the sham surgery group. Conclusions Our findings suggest that the development of pulmonary arterial hypertension in CKD-PH rats is likely a consequence of a combined effect: RAAS dysregulation, decreased ACE2 expression in pulmonary vascular endothelial cells, and metabolic disturbances. Graphical Abstract

Abstract This paper sets out to develop an efficient probabilistic optimal power flow (POPF) algorithm to assess the influence of wind power on power grid. Given a set of wind data at multiple sites, their marginal distributions are fitted by a newly developed generalized Johnson system, whose parameters are specified by a percentile matching method. The correlation of wind speeds is characterized by a flexible Liouville copula, which allows to model the asymmetric dependence structure. In order to improve the efficiency for solving POPF problem, a lattice sampling method is developed to generate wind samples at multiple sites, and a logistic mixture model is proposed to fit distributions of POPF outputs. Finally, case studies are performed, the generalized Johnson system is compared with Weibull distribution and the original Johnson system for fitting wind samples, Liouville copula is compared against Archimedean copula for modelling correlated wind samples, and lattice sampling method is compared with Sobol sequence and Latin hypercube sampling for solving POPF problem on IEEE 118‐bus system, the results indicate the higher accuracy of the proposed methods for recovering the joint cumulative distribution function of correlated wind samples, as well as the higher efficiency for calculating statistical information of POPF outputs.

Abstract Background Prompt and precise differential diagnosis of biliary atresia (BA) among cholestatic patients is of great importance. Matrix metalloproteinase-7 (MMP-7) holds great promise as a diagnostic marker for BA. This study aimed to investigate the accuracy of age-specific serum MMP-7 for discriminating BA from other cholestatic pediatric patients. Methods This was a single center diagnostic accuracy and validation study including both retrospective and prospective cohorts. Serum MMP-7 concentrations were measured using an ELISA kit, the trajectory of which with age was investigated in a healthy infants cohort aged 0 to 365 days without hepatobiliary diseases (n = 284). Clinical BA diagnosis was based on intraoperative cholangiography and subsequent histological examinations. The diagnostic accuracy of age-specific cutoffs of serum MMP-7 were assessed in a retrospective cohort of cholestatic patients (n = 318, with 172 BA) and validated in a prospective cohort (n = 687, including 395 BA). Results The MMP-7 concentration declines non-linearly with age, showing higher levels in healthy neonates as well as higher cutoff value in neonatal cholestasis. The area under the ROC curve (AUROC) was 0.967 (95% confidence interval [CI]: 0.946–0.988) for the retrospective cohort, and the cutoff of 18 ng/mL yielded 93.0% (95%CI: 88.1-96.3%), 93.8% (95%CI: 88.6-97.1%), 94.7% (95%CI: 90.1-97.5%), and 91.9% (95%CI: 86.4-95.8%) for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), respectively. The performance of MMP-7 was successfully validated in the larger prospective cohort, resulting in a diagnostic sensitivity of 95.9% (379/395; 95% CI: 93.5–97.7%), a specificity of 87.3% (255/292; 95% CI: 83.0–90.9%), a PPV of 91.1% (379/416; 95% CI: 87.9–93.7%), and a NPV of 94.1% (255/271; 95% CI: 90.6–96.6%), respectively. Besides, higher cutoff value of 28.1 ng/mL achieved the best sensitivity, specificity, PPV, and NPV for infants aged 0–30 days, which was 86.4% (95% CI: 75.0–94.0%), 95.5% (95% CI: 77.2–99.9%), 98.1% (95% CI: 89.7–100%), and 72.4% (95% CI: 52.8–87.3%), respectively. Conclusions The serum MMP-7 is accurate and reliable in differentiating BA from non-BA cholestasis, showing its potential application in the diagnostic algorithm for BA and significant role in the future research regarding pathogenesis of BA.

Summary: Background: Dengue remains a global threat to public health, however, its disease burden among children and adolescents has always been poorly quantified. Therefore, we aimed to systematically estimate the global, regional, and national burden and temporal trends of dengue infection in children and adolescents from 1990 to 2021. Methods: Data on the number and rate of incidence and disability-adjusted life-years (DALYs) of dengue infection among children and adolescents under 20 years were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) of the age-standardised incidence rate (ASIR) and age-standardised DALYs rate (ASDR), by age, sex, and different countries and regions, were calculated to quantify the temporal trends of dengue burden. The association between development levels (measured using the socio-demographic index [SDI]) and dengue burden was also determined. Findings: From 1990 to 2021, the global burden of dengue incidence and its associated DALYs was consistently higher in children and adolescents than in the entire population. Globally, among children and adolescents, there were 21,641,016 incident cases in 2021, an increase of 64.43% compared to 13,241,719 in 1990. The ASIR per 100,000 population increased from 587.81 in 1990 to 812.16 in 2021, with an EAPC of 1.39% (95% confidence interval [CI], 1.13%–1.65%). Besides, the number of dengue-associated DALYs among children and adolescents increased by 16.36%, from 910,458.60 in 1990 to 1,059,428.31 in 2021. The increase in DALYs was less pronounced than incidence, with the ASDR per 100,000 population increasing from 40.17 in 1990 to 41.50 in 2021, and the EAPC was only 0.67% (95% CI, 0.40%–0.95%). The incidence and DALYs burden of dengue in children and adolescents was highest in middle SDI regions, followed by low-middle SDI regions, with the lowest burden in high SDI regions. Furthermore, Tropical Latin America had an extremely high ASIR (6040.29 per 100,000 population in 2021), and Southeast Asia had an extremely high ASDR (298.20 per 100,000 population in 2021), much higher than other regions around the world. Interpretation: The global dengue burden in children and adolescents is high and has been increasing from 1990 to 2021, even though the distribution patterns vary across different countries and territories. This study first reported the global disease burden and temporal trends of children and adolescents, which has significant implications for policymakers and public health officials, as it underscores the need for age- and region-specific strategies to mitigate the growing global burden of dengue. Funding: National Natural Science Foundation of China.

Summary: Background: Over 40% of pregnant women in the USA are obese which negatively affects fetal development and offspring health. Maternal obesity (MO) leads to fibrotic infiltration in multiple tissues and organs of offspring during their adulthood although the origin and mechanisms are unclear. Methods: C57BL/6J female mice were fed a control and high-fat diet to mimic MO condition. Embryonic somatic tissues were obtained at E9.5, E11.5, and E13.5 (equivalent to 6 weeks of human pregnancy) from control (CON) and MO mice for single-cell RNA-sequencing (scRNA-seq). To explore the role of AMP-activated protein kinase (AMPK), AMPK was activated by metformin and A769662, and knocked out in embryonic mesenchymal cells (EMC) using AMPKα1 floxed mice. Findings: Using unsupervised clustering, we identified three major cell populations with fibrogenic capacity. Compared to CON, the population of fibrogenic cells increased dramatically (by ∼125%) due to MO, supporting an embryonic origin of fibrosis in the offspring. MO induced inflammatory response and elevated expression of transforming growth factor β (TGFβ) signalling and fibrogenic genes in embryos. MO inhibited AMPK and its activation by metformin and A769662 inhibited TGFβ signalling and fibrogenesis. Interpretation: MO profoundly enhances embryonic fibrogenesis, explaining the origin of fibrosis in the offspring of mothers living with obesity. Our data underscore the importance of early intervention, before 5–6 weeks of pregnancy, in improving embryonic development, and AMPK is an amiable target for suppressing excessive fibrogenesis in MO embryos to assist increasing populations of obese mothers having healthy children. Funding: This work was funded by National Institutes of Health Grant R01HD067449.

Inflammatory bowel disease (IBD) is characterized by disturbances in intestinal flora and metabolomic profiles. Building on previous findings that purple potato (PP) supplementation suppresses inflammation and restores intestinal barrier in dextran sulfate sodium (DSS)-treated mice, this study examined changes in the fecal metabolome in the same cohort. Mice were fed 0 % or 10 % PP for 7 weeks, with DSS administered in the fifth week of dietary treatment followed by one-week normal drinking water recovery. A total of 68 metabolites, including amino acids, fatty acids, organic acids, carbohydrates, and polyamines, were significantly altered across the groups. PP supplementation reversed changes in 13 of the 25 DSS-altered metabolites. Six microbial metabolites derived from PP polyphenols were identified and positively correlated with M2 macrophage polarization. Data suggest that dietary PP is effective in reducing inflammation and improves gut metabolites in DSS-induced colitis mice, offering a potential dietary therapy for managing IBD.

As people live longer, the burden of aging-related brain diseases, especially dementia, is increasing. Brain aging increases the risk of cognitive impairment, which manifests as a progressive loss of neuron function caused by the impairment of synaptic plasticity via disrupting lipid homeostasis. Therefore, supplemental dietary lipids have the potential to prevent brain aging. This review summarizes the important roles of dietary lipids in brain function from both structure and mechanism perspectives. Epidemiological and animal studies have provided evidence of the functions of polyunsaturated fatty acids (PUFAs) in brain health. The results of interventions indicate that phospholipids—including phosphatidylcholine, phosphatidylserine, and plasmalogen—are efficient in alleviating cognitive impairment during aging, with plasmalogen exhibiting higher efficacy than phosphatidylserine. Plasmalogen is a recognized nutrient used in clinical trials due to its special vinyl ether bonds and abundance in the postsynaptic membrane of neurons. Future research should determine the dose-dependent effects of plasmalogen in alleviating brain-aging diseases and should develop extraction and storage procedures for its clinical application.

Abstract Background Environmental factors greatly impact infectious disease-related mortality, yet there's a lack of comprehensive global studies on the contemporary burden and trends. This study aims to evaluate the global burden and trends of infectious disease mortality caused by air pollution, unsafe water, poor sanitation, and non-optimal temperature across Socio-Demographic Index (SDI) regions from 1990 to 2019. Methods This observational study utilized data from the Global Burden of Diseases Study to examine mortality rates from infectious diseases attributed to environmental risk factors between 1990 and 2019, including air pollution, unsafe water, sanitation, handwashing facilities (UWSH), and non-optimal temperatures. Age-standardized mortality rates (ASMRs) and estimated annual percentage change (EAPC) were utilized to present infectious disease mortality, and its trajectory influenced by environmental risk factors over the years. Nonlinear regression was conducted to explore the association between the SDI and ASMRs across regions from 1990 to 2019. Results In 2019, global infectious disease deaths linked to air pollution, UWSH, and non-optimal temperature reached a startling 2,556,992. Disease mortality varied widely across SDI regions, with the highest number of deaths due to air pollution and UWSH in Low SDI regions, and deaths from non-optimal temperature primarily in High SDI regions. Age disparities emerged, with children under five and the elderly most affected. However, an increasing mortality trend was observed among seniors (65–69, 75–79, and over 80) in High SDI regions due to enteric infections linked to UWSH. Globally, a consistent decrease in ASMR was seen from 1990 to 2019 for all diseases connected to these factors, except for respiratory infections linked to non-optimal temperature. Conclusions Our study underscores the significant impact of air pollution, UWSH, and non-optimal temperatures on global infectious disease mortality, particularly among vulnerable groups such as children and the elderly. It's important to tackle these challenges with targeted interventions aiming to enhance environmental quality, improve water and sanitation systems, and control extreme temperatures. In addition, international cooperation is essential for bridging regional disparities and driving global public health initiatives forward, thereby helping achieve Sustainable Development Goals more effectively.

Objective To identify the effective components and key molecules of Yiqi Huoxu compound(YQHX) in the treatment of pulmonary inflammation and fibrosis in scleroderma, providing basis for the development of drug targets for scleroderma. Methods A mouse model of pulmonary fibrosis was established by a single tracheal perfusion of bleomycin. Twenty-four mice were randomly divided into four groups, i.e. intragastric PBS, bleomycin alone, intragastric Yiqi Huoxue compound, and control. HE staining and Masson staining were used to verify the therapeutic effect of Yiqi Huoxue compound on lung inflammation and fibrosis. The active components and target genes of anti-fiber salvia miltiorrhiza were obtained from TCMSP database. PPI network, GO/KEGG enrichment analysis, molecular docking and other bioinformatics analyses were integrated to identify the main active ingredients and key targets of salvia miltiorrhiza in the treatment of scleroderma, and to analyze the relevant signaling pathways. The expression levels of CD3 antibody, p-PI3K antibody and p-AKT antibody were analyzed by immunohistochemistry to verify the effects of Yiqi Huoxu compound on inflammation and key pathways. Results The results of HE staining and Masson staining showed that the severity of fibrosis and inflammatory infiltration were decreased, suggesting that Yiqi Huoxue compound could significantly improve the pulmonary fibrosis, inflammation and tissue damages. The key component of salvia miltiorrhiza was mainly luteolin. PPI network analysis showed that AKT1, EGFR, ESR1, TNF and IL6 were the core targets of salvia miltiorrhiza in the treatment of scleroderma. KEGG enrichment analysis showed that the genes were mainly enriched in the PI3K-AKT pathway. Molecular docking analysis showed the potential binding sites between luteolin and four key targets. The immunohistochemical results showed that YQHX significantly decreased bleomycin-induced CD3+T cell infiltration, p-PI3K and p-AKT levels in mouse lung tissue. Conclusions YQHX has significant therapeutic effects on lung inflammation and fibrosis. Luteolin may be a key effective molecule in YQHX, and treat scleroderma lung inflammation and fibrosis by targeting the PI3K-AKT pathway.

The effect of sulfides on the pitting corrosion behavior and film chemistry of 70/30 copper-nickel alloys in aerated seawater was investigated. Sulfides in seawater prevent the formation of protective oxides on the surface of the alloy and alter the morphology and composition of the corrosion products. It results in the corrosion product film consisting of the double layer structure of the loose and porous sulfide-containing outer layer and the dense inner layer. This double-layer structure of the corrosion product film can't alleviate corrosion, but instead accelerates the development of pitting corrosion. The statistical analysis method is used to study the corrosion process of 70/30 copper-nickel alloy in sulfide-containing environment. This work records the trend of pitting corrosion towards the horizontal and longitudinal directions.

Objectives To estimate the interaction between economic status (ES) and healthy lifestyle in long COVID among Chinese older people infected with SARS-CoV-2.Design A cross-sectional study based on the Peking University Health Cohort in Anning, Yunnan.Setting All primary health institutions in Anning, Yunnan Province, China, from April to May 2023.Participants A total of 4804 people aged 60 and older infected with SARS-CoV-2 were included in this study.Primary and secondary outcome measures Long COVID was measured by participants’ self-reported symptoms using structured questionnaires. ES was measured by last-month personal income, and participants’ ES was defined as low if their income was below the per capita monthly income of local residents. Lifestyle score was equal to the number of healthy behaviours (including smoking, drinking, weight, exercise and diet) and grouped using the median score as the cut-off point. Univariate and multivariate logistic models were employed to estimate the association of ES with long COVID. Interaction between ES and lifestyle in long COVID was assessed by multiplicative interaction term.Results We enrolled a total of 4804 participants infected with SARS-CoV-2, of whom 57.3% (2754 of 4804) had at least one long COVID symptom. Fatigue (1546, 56.1%), cough (1263, 45.9%) and muscle pain (880, 32.0%) were the top three common symptoms. Patients with low ES had a 48% (adjusted OR: 1.48; 95% CI 1.22, 1.82) increased risk of long COVID. A significant interaction was observed between ES and lifestyle (p value for interaction

IntroductionEnterotoxigenic Escherichia coli (ETEC) is the main diarrhea-causing pathogen in children and young animals and has become a global health concern. Berberine is a type of “medicine and food homology” and has a long history of use in China, particularly in treating gastrointestinal disorders and bacterial diarrhea.MethodsIn this study, we explored the effects of berberine on growth performance, intestinal inflammation, oxidative damage, and intestinal microbiota in a weaned piglet model of ETEC infection. Twenty-four piglets were randomly divided into four groups—a control group (fed a basal diet [BD] and infused with saline), a BD+ETEC group (fed a basal diet and infused with ETEC), a LB+ETEC group (fed a basal diet with 0.05% berberine and infused with ETEC infection), and a HB+ETEC group (fed a basal diet with 0.1% berberine and infused with ETEC).ResultsBerberine significantly improved the final body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI) (P

Abstract BackgroundRecently, the growing demand for pediatric sedation services outside the operating room has imposed a heavy burden on pediatric centers in China. There is an urgent need to develop a novel system for improved sedation services. ObjectiveThis study aimed to develop and implement a computerized system, the Pediatric Sedation Assessment and Management System (PSAMS), to streamline pediatric sedation services at a major children’s hospital in Southwest China. MethodsPSAMS was designed to reflect the actual workflow of pediatric sedation. It consists of 3 main components: server-hosted software; client applications on tablets and computers; and specialized devices like gun-type scanners, desktop label printers, and pulse oximeters. With the participation of a multidisciplinary team, PSAMS was developed and refined during its application in the sedation process. This study analyzed data from the first 2 years after the system’s deployment. Implementation (Results)From January 2020 to December 2021, a total of 127,325 sedations were performed on 85,281 patients using the PSAMS database. Besides basic variables imported from Hospital Information Systems (HIS), the PSAMS database currently contains 33 additional variables that capture comprehensive information from presedation assessment to postprocedural recovery. The recorded data from PSAMS indicates a one-time sedation success rate of 97.1% (50,752/52,282) in 2020 and 97.5% (73,184/75,043) in 2021. The observed adverse events rate was 3.5% (95% CI 3.4%‐3.7%) in 2020 and 2.8% (95% CI 2.7%-2.9%) in 2021. ConclusionsPSAMS streamlined the entire sedation workflow, reduced the burden of data collection, and laid a foundation for future cooperation of multiple pediatric health care centers.

This study explored the benefits of purple potatoes against colitis in IL-10-deficient mice. Mice were fed either a standard diet or one supplemented with 10 % purple potato for 11 weeks. The results demonstrated that purple potato intake notably improved colitis symptoms and pathobiological scores. It induced significant changes in the gut bacteria, reducing harmful phyla associated with colitis, Proteobacteria and Deferribacteres, while increasing beneficial phyla, Firmicutes and Tenericutes. It increased the abundance of Bifidobacteriaceae, Porphyromonadaceae, and Lachnospiraceae-Ruminococcaceae, a major butyrate-producing group while decreasing bacterial families commonly elevated in IBD patients, including Bacteroidaceae, Sutterellaceae, Coriobacteriaceae, Enterobacteriaceae, and Peptostreptococcaceae. Additionally, purple potatoes boosted intestinal integrity, evidenced by increased goblet cell density and enhanced expression of key markers in maintaining gut health. Furthermore, they promoted mitochondrial function and reduced levels of inflammatory cytokines. Collectively, purple potatoes show promise in protecting against colitis through their effects on gut microbiota, intestinal integrity, and oxidative function.

The melting impacts on the three-dimensional hybrid nanofluid flow by a stationary stretching disk is examined. The flow configuration is due to the stretching of the disk. The magnetic field is applied normal to the disk in order to generate the resistance in the liquid. The performance of heat transfer in the liquid, the thermal radiation and heat generation/absorption impacts are taken into consideration. The melting heat transfer impact on the surface is analyzed here. The impact of stretching and rotating mechanisms along with applied physical impacts on the hybrid nanofluid flow and heat features are of the present concern for this physical problem. A conventional transformation is presented to lead to a set of coupled similarity equations which are highly non-linear in nature. A numerical method subject to bvp4c technique is adopted for the solution process. Results reveal that increasing trend of stretching of the disk lowers the boundary layer thickness and consequently highers the rate of heat transfer. It is found the reduction in thickness of thermal boundary layer by the strength of stretching. Additionally, the temperature distribution rises by the influence of melting temperature. Further, the skin fraction coefficient seen to be enhanced with the enlargement of nanoparticles volume fraction.

Abstract Background This study aimed to evaluate the effect of sacubitril valsartan (SV) on heart failure (HF) hospitalization and cardiovascular mortality in patients on hemodialysis with HF with preserved ejection fraction (EF; HFpEF). Methods This single-center, prospective study enrolled 155 stable hemodialysis patients with EF > 40% who were followed up for 12 months. Fifty-nine patients were treated with SV; the others were matched for EF (57.89 ± 9.35 vs. 58.00 ± 11.82, P = 0.9) at a ratio of 1:1 and included as controls. The target dosage of SV was 200 mg/day. Results Twenty-three (23/155; 14.84%) had HF with mid-range EF (HFmrEF), while 132 (85.16%) had HFpEF. After SV treatment, the peak early diastolic transmitral flow velocity/peak early diastolic mitral annular tissue velocity(E/e’) improved from 17.19 ± 8.74 to 12.80 ± 5.52 (P = 0.006), the left ventricular (LV) end-diastolic diameter decreased from 53.14 ± 7.67 mm to 51.56 ± 7.44 mm (P = 0.03), and the LV mass index decreased from 165.7 ± 44.6 g/m2 to 154.8 ± 24.0 g/m2 (P = 0.02). LVEF (P = 0.08) and LV global longitudinal strain (P = 0.7) did not change significantly. The composite outcome of first and recurrent HF hospitalization or cardiovascular death showed no difference between group. However, the Acute Dialysis Quality Initiative Workgroup (ADQI) HF class improved in 39 and 15 patients and worsened in 1 and 11 patients in the SV and control groups, respectively (P 40%.

ABSTRACT: The main purpose of the current study was to investigate the ameliorative effects of bovine milk osteopontin (bmOPN) on the gut dysfunction of pregnant rats fed a high-fat diet (HFD). Bovine milk osteopontin was supplemented at a dose of 6 mg/kg body weight. Bovine milk osteopontin supplementation during pregnancy reduced colonic inflammation of HFD dams, and it also increased the colonic expression of ZO-1 and claudin-4 of HFD dams. Bovine milk osteopontin significantly enriched the relative abundance of Bacteroidetes, whereas it decreased Proteobacteria, Helicobacteraceae, and Desulfovibrionaceae in feces of HFD dams. The levels of isobutyric acid and pentanoic acid in the HFD + bmOPN group were higher than that of the HFD group. Functional predication analysis of microbial genomes revealed that bmOPN supplementation to HFD pregnancies changed 4 Kyoto Encyclopedia of Genes and Genomes pathways including bile acid biosynthesis. Further, bmOPN enriched hepatic taurochenodeoxycholic acid and tauroursodeoxycholic acid plus taurohyodeoxycholic acid in the gut of HFD maternal rats. Our findings suggested that bmOPN improved the gut health of HFD pregnant rats partially through modulating bile acid biosynthesis.

Abstract Background The associations between trajectories of different health conditions and cognitive impairment among older adults were unknown. Our cohort study aimed to investigate the impact of various trajectories, including sleep disturbances, depressive symptoms, functional limitations, and multimorbidity, on the subsequent risk of cognitive impairment. Methods We conducted a prospective cohort study by using eight waves of national data from the Health and Retirement Study (HRS 2002–2018), involving 4319 adults aged 60 years or older in the USA. Sleep disturbances and depressive symptoms were measured using the Jenkins Sleep Scale and the Centers for Epidemiologic Research Depression (CES-D) scale, respectively. Functional limitations were assessed using activities of daily living (ADLs) and instrumental activities of daily living (IADLs), respectively. Multimorbidity status was assessed by self-reporting physician-diagnosed diseases. We identified 8-year trajectories at four examinations from 2002 to 2010 using latent class trajectory modeling. We screened participants for cognitive impairment using the 27-point HRS cognitive scale from 2010 to 2018 across four subsequent waves. We calculated hazard ratios (HR) using Cox proportional hazard models. Results During 25,914 person-years, 1230 participants developed cognitive impairment. In the fully adjusted model 3, the trajectories of sleep disturbances and ADLs limitations were not associated with the risk of cognitive impairment. Compared to the low trajectory, we found that the increasing trajectory of depressive symptoms (HR = 1.39; 95% CI = 1.17–1.65), the increasing trajectory of IADLs limitations (HR = 1.88; 95% CI = 1.43–2.46), and the high trajectory of multimorbidity status (HR = 1.48; 95% CI = 1.16–1.88) all posed an elevated risk of cognitive impairment. The increasing trajectory of IADLs limitations was associated with a higher risk of cognitive impairment among older adults living in urban areas (HR = 2.30; 95% CI = 1.65–3.21) and those who smoked (HR = 2.77; 95% CI = 1.91–4.02) (all P for interaction

Abstract Although acute kidney injury (AKI) is a frequent postoperative complication after liver transplantation, renal function following living‐related liver transplantation (LRLT) in infants remains understudied. The aim of this study was to identify the prevalence of AKI and the impact of AKI on outcomes in infant recipients with biliary atresia. We retrospectively reviewed infants who underwent LRLT surgery between January 2018 and January 2021. The primary outcome was the risk of postoperative AKI occurrence in the first 7 postoperative days. A multivariate regression analysis model was used to investigate risk factors for AKI, and the incidence and impacts of AKI on outcomes were analyzed. A total of 98 patients were included in the analysis. AKI occurred in 59 patients (60.2%) within 7 days after surgery. Logistic regression analysis revealed that preoperative transfusion (p < 0.05) and lower serum creatinine (SCr) (p < 0.05) were independent risk factors for AKI. The incidence of serious complications was significantly higher in the AKI group than in the non‐AKI group (p < 0.05). The postoperative mechanical ventilation time (p < 0.05) and hospital stay (p = 0.019) were significantly longer in the AKI group. There was no evidence of chronic kidney disease (CKD) in any surviving infants within 1 year after surgery. In conclusion, AKI is common in infant LRLT (60.2%), and preoperative transfusion and lower SCr levels were independently associated with AKI. AKI may be associated with the incidence of serious complications, prolonged use of ventilators, and hospital stays. No CKD occurred within 1 year.

We aimed to assess the impact of vitamin A supplementation in beef cows at late gestation on intramuscular adipogenesis in the offspring. Thirty pregnant beef cows were randomly assigned to a control group (CON; n = 15) fed a diet containing 4.1 KIU of vitamin A per kilogram, and to a vitamin A–supplemented group (VITA; n =15) fed a diet containing 12.2 KIU of vitamin A per kilogram. The treatment application occurred from 180 d of gestation until parturition. Calves were biopsied within 10 d of age to collect skeletal muscle samples for assessing gene expression and protein abundance of target genes/proteins related to adipogenesis. All calves were raised under the same conditions until slaughter at 479 ± 1.6 d of age. Cows from both treatments showed no differences (P > 0.05) in total gain and final body weight, although CON cows tended to exhibit greater (P = 0.06) dry matter intake. Skeletal muscle of newborns from the VITA group exhibited increased mRNA expression of retinoic acid receptor β (RARβ; P = 0.05), whereas no differences (P > 0.05) were observed in mRNA expression of markers for fibroadipogenic progenitor cells (PDGFRα) and adipogenesis (ZFP423 and PPARγ). However, skeletal muscle of newborns from the VITA group showed greater protein abundance of DLK1 (P < 0.01) and PPARγ (P = 0.03) than those from the CON group. No differences (P > 0.05) among treatments were observed in the abundance of retinoid X receptor and PDGFRα . Repeated carcass ultrasound measurements of the offspring showed increased intramuscular fat content throughout all the evaluated stages of their post-natal life (P < 0.05), while no changes were observed within subcutaneous fat measurements (P > 0.05). Hot carcass weight, carcass yield and dressing percentage, and kidney pelvic heart (KPH) fat percentage were not affected by treatment (P > 0.05). These findings suggest that vitamin A supplementation during late gestation enhances intramuscular adipogenesis in offspring.

Abstract Due to the exclusive maternal transmission, oocyte mitochondrial dysfunction reduces fertility rates, affects embryonic development, and programs offspring to metabolic diseases. However, mitochondrial DNA (mtDNA) are vulnerable to mutations during oocyte maturation, leading to mitochondrial nucleotide variations (mtSNVs) within a single oocyte, referring to mtDNA heteroplasmy. Obesity (OB) accounts for more than 40% of women at the reproductive age in the USA, but little is known about impacts of OB on mtSNVs in mature oocytes. It is found that OB reduces mtDNA content and increases mtSNVs in mature oocytes, which impairs mitochondrial energetic functions and oocyte quality. In mature oocytes, OB suppresses AMPK activity, aligned with an increased binding affinity of the ATF5‐POLG protein complex to mutated mtDNA D‐loop and protein‐coding regions. Similarly, AMPK knockout increases the binding affinity of ATF5‐POLG proteins to mutated mtDNA, leading to the replication of heteroplasmic mtDNA and impairing oocyte quality. Consistently, AMPK activation blocks the detrimental impacts of OB by preventing ATF5‐POLG protein recruitment, improving oocyte maturation and mitochondrial energetics. Overall, the data uncover key features of AMPK activation in suppressing mtSNVs, and improving mitochondrial biogenesis and oocyte maturation in obese females.

Abstract

Abstract Background Stroke is a major cause of acute neurological symptoms in children with significant long-term neurological sequelae. However, data of diseases burden on stroke among children was lack. We aimed to be dedicated to analyze and compare global trends as well as regional and sociodemographic differences in stroke prevalence, incidence, mortality and disability-adjusted life-years (DALYs) among children aged 0 ~ 14 years. Method We obtained data on annual number of incident strokes, prevalent strokes, deaths, and DALYs, age-standardized incidence rates (ASIRs), prevalence rates (ASPRs), mortality rates (ASMRs) and DALY rates (ASDRs) of stroke among individuals aged 14 years and younger during 1990–2019 from the 2019 Global Burden of Disease Study. To quantify the temporal trends, we calculated changes (%) in number, and used joinpoint regression analysis to identify the average annual percentage changes (AAPCs) of age standardized rates. Result Globally, the incident strokes and prevalent strokes increased by 18.51% and 31.97%, respectively, but DALYs due to stroke and deaths due to stroke decreased by 60.18% and 65.03%, respectively, from 1990 to 2019. During the same period, ASIR increased by 0.21% (95%CI: 0.17, 0.24) from 18.02 to 100,000 population in 1990 to 19.11 per 100,000 in 2019; ASPR increased by 0.66% (95%CI: 0.36, 0.96) from 68.88 to 100,000 population in 1990 to 81.35 per 100,000 in 2019; while ASMR (AAPC= -3.94; 95%CI: -4.07, -3.81) and ASDR (AAPC= -3.50; 95%CI: -3.64, -3.36) both decreased. In 2019, the highest age standardized incidence, prevalence, mortality, and DALY rates all occurred in low sociodemographic index (SDI) regions. The greatest increase of age standardized incidence rate (AAPC = 0.21; 95%CI: 0.18, 0.25) and prevalence rate (AAPC = 1.15; 95%CI: 0.34, 1.96) both were in high SDI regions. Eastern Sub-Saharan Africa had the highest ASIR and ASPR in 2019, and Oceania had the highest ASMR and ASDR in 2019 across 21 GBD regions. High-income North America had the largest increase in ASIR (AAPC = 0.63; 95%CI: 0.59, 0.66) and ASPR (AAPC = 1.58; 95%CI: 0.54, 2.63). Against the overall decreasing trend of ASMR, an increasing trend of ASMR was found in Zimbabwe (AAPC = 0.91; 95%CI: 0.44, 1.37) and Botswana (AAPC = 0.74; 95%CI: 0.02, 1.47). Conclusion The overall increasing stroke incidence and prevalence indicated that prevention and management of stroke among younger population should be critical in the future. Despite stroke mortality with falling trend worldwide, specific countries or territories present worrying increase in stroke mortality. Without urgent implementation of effective primary prevention strategies, the stroke burden of children will probably continue to grow across the world, particularly in high-SDI countries.

This study aims to investigate the stratigraphic features and rare earth element (REE) mechanisms of deep-sea REE-rich sediments in the West Pacific Pigafetta Basin using acoustic rapid detection technology. Through an analysis of sub-bottom profile data and synthesis of existing studies, this study reveals the acoustic properties and thickness distribution of the REE-rich sediments. Acoustic spectral records identify three distinct acoustic facies: opaque (O), transparent (T), and laminated (L). This study maps the thickness and spatial distribution of the REE-rich sediment layer in the research area, ranging from approximately 6 to 36 m in thickness. Regions with REE-rich sediments exceeding 30 m in depth are identified, showing concentrated distribution along the northwest–southeast axis and a contiguous zone in the southwest corner of the study area. The method employed in this study can determine the potential bottom boundary of the REE-rich layer by assessing the thickness range of the sedimentary layer, overcoming limitations of traditional sampling methods. Furthermore, the thickness distribution characteristics of the REE-rich sedimentary layer in the study area provide valuable insights for future research on resource evaluation and estimation.

Abstract Right heart failure is the leading cause of death in pulmonary hypertension (PH), and echocardiography is a commonly used tool for evaluating the risk hierarchy of PH. However, few studies have explored the dynamic changes in the structural and functional changes of the right heart during the process of PH. Previous studies have found that pulmonary circulation coupling right ventricular adaptation depends on the degree of pressure overload and other factors. In this study, we performed a time-dependent evaluation of right heart functional changes using transthoracic echocardiography in a SU5416 plus hypoxia (SuHx)-induced PH rat model. Rats were examined in 1-, 2-, 4-, and 6-week using right-heart catheterization, cardiac echocardiography, and harvested heart tissue. Our study found that echocardiographic measures of the right ventricle (RV) gradually worsened with the increase of right ventricular systolic pressure, and right heart hypofunction occurred at an earlier stage than pulmonary artery thickening during the development of PH. Furthermore, sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2), a marker of myocardial damage, was highly expressed in week 2 of SuHx-induced PH and had higher levels of expression of γ-H2AX at all timepoints, as well as higher levels of DDR-related proteins p-ATM and p53/p-p53 and p21 in week 4 and week 6. Our study demonstrates that the structure and function of the RV begin to deteriorate with DNA damage and cellular senescence during the early stages of PH development.

Sleep disturbances are highly prevalent during the COVID-19 pandemic, especially among older adults. We aimed to evaluate sleep heath during COVID-19 pandemic and assess the differences among geographical regions and pandemic periods. We searched three databases (PubMed, Embase, Web of Science) to find articles up to March 12, 2023. We included observational studies that reported the prevalence of sleep disturbances among adults aged 60 years or older in any setting. Two researchers independently reviewed the literature and retrieved the data. We used Der Simonian-Laird random effects meta-analyses to pool the data, followed by subgroup analysis, sensitivity analysis, and meta-regression. A total of 64 studies with 181,224 older adults during the pandemic were included. The prevalence of poor sleep quality, short sleep duration, long sleep duration, and insomnia symptoms were 47.12% (95% CI: 25.97%, 68.27%), 40.81% (95% CI: 18.49%, 63.12%), 31.61% (95% CI: 24.83%, 38.38%), and 21.15% (95% CI: 15.30%, 27.00%), respectively. The prevalence of sleep problems reported by self-constructed items was 26.97% (95% CI: 20.73%, 33.22%). When compared to America (64.13%), Europe (20.23%) and the Western Pacific (21.31%) showed a lower prevalence of sleep problems (all P

DNA methylation is influenced by various exogenous factors such as nutrition, temperature, toxicants, and stress. Bulls from the Pacific Northwest region of the United States and other northern areas are exposed to extreme cold temperatures during winter. However, the effects of cold exposure on the methylation patterns of bovine sperm remain unclear. To address, DNA methylation profiles of sperm collected during late spring and winter from the same bulls were analyzed using whole genome bisulfite sequencing (WGBS). Bismark (0.22.3) were used for mapping the WGBS reads and R Bioconductor package DSS was used for differential methylation analysis. Cold exposure induced 3,163 differentially methylated cytosines (DMCs) with methylation difference ≥10% and a q-value < 0.05. We identified 438 differentially methylated regions (DMRs) with q-value < 0.05, which overlapped with 186 unique genes. We also identified eight unique differentially methylated genes (DMGs) (Pax6, Macf1, Mest, Ubqln1, Smg9, Ctnnb1, Lsm4, and Peg10) involved in embryonic development, and nine unique DMGs (Prmt6, Nipal1, C21h15orf40, Slc37a3, Fam210a, Raly, Rgs3, Lmbr1, and Gan) involved in osteogenesis. Peg10 and Mest, two paternally expressed imprinted genes, exhibited >50% higher methylation. The differential methylation patterns of six distinct DMRs: Peg10, Smg9 and Mest related to embryonic development and Lmbr1, C21h15orf40 and Prtm6 related to osteogenesis, were assessed by methylation-specific PCR (MS-PCR), which confirmed the existence of variable methylation patterns in those locations across the two seasons. In summary, cold exposure induces differential DNA methylation patterns in genes that appear to affect embryonic development and osteogenesis in the offspring. Our findings suggest the importance of replicating the results of the current study with a larger sample size and exploring the potential of these changes in affecting offspring development.

Background: The burden of neonatal infections in low- and middle-income countries and territories (LMICs) is a critical public health challenge, while our understanding of specific burden and secular trends remains limited. Methods: We gathered annual data on 15 types of neonatal infections in LMICs from 1990 to 2019 from the Global Burden of Disease 2019. Numbers, rates, percent changes, and estimated annual percentage changes of incidence and deaths were calculated. We also explored the association between disease burden, socio-demographic index (SDI), and universal health coverage index (UHCI). Results: Enteric infections and upper respiratory infections owned the top highest incidence rates for neonates in 2019. Neonatal sepsis and other neonatal infections, as well as otitis media, demonstrated an increasing trend of incidence across all 3 low- and middle-income regions. The top 3 causes of neonatal mortality in 2019 were neonatal sepsis and other neonatal infections, lower respiratory infections, and enteric infections. Between 1990 and 2019, all of the neonatal infection-related mortality rates suggested an overall decline. Sex differences could be found in the incidence and mortality of some neonatal infections, but most disease burdens decreased more rapidly in males. SDI and UHCI were both negatively associated with most of the disease burden, but there were exceptions. Conclusions: Our study serves as a vital exploration into the realities of neonatal infectious diseases in LMICs. The identified trends and disparities not only provide a foundation for future research but also underscore the critical need for targeted policy initiatives to alleviate on a global scale.

Abstract Objective We aimed to investigate the association between visit‐to‐visit heart rate variability (VVHRV) and all‐cause mortality in patients diagnosed with atrial fibrillation (AF). Previous studies have shown a positive correlation between VVHRV and several adverse outcomes. However, the relationship between VVHRV and the prognosis of AF remains uncertain. Methods In our study, we aimed to examine the relationship between VVHRV and mortality rates among 3983 participants with AF, who were part of the AFFIRM study (Atrial Fibrillation Follow‐Up Investigation of Rhythm Management). We used the standard deviation of heart rate (HRSD) to measure VVHRV and divided the patients into four groups based on quartiles of HRSD (1st,